This research proposal is directed at elucidating the mechanism of action of steroid hormones on bone cells. Bone is a clinically important target for glucocorticoids and possibly for other steroid hormones such as estrogens, androgens, and Vitamin D metabolites. The proposal attempts to define the mechanisms by which glucocorticoids effect bone cell function and thereby gain insight into the pathophysiology of glucocorticoid induced osteoporosis. In a similar fashion, the project is directed at elucidating the nature of estrogen mediated effects on bone cells to better understand the potential role of the sex steroids on bone homeostasis. The system to be employed is a primary monolayer culture of bone cells obtained from fetal rat calvaria by collagenase digestion. As detailed in the subsequent pages of the proposal, three related lines of inquiry will be pursued: 1) to ascertain whether receptors for a variety of steroid hormones are present in bone cells; 2) to elucidate the effects of steroids on bone cell proliferation and differentiation, cyclic AMP accumulation and citrate metabolism; and 3) to examine the interaction of steroid hormones with other regulators of bone cell function parathyroid hormone, prostaglandins and Vitamin D metabolites. A multi-phasic experimental design is planned subjecting several different but related aspects of steroid action to investigation. It is hoped that the interrelationships developed by this approach will significantly add to our understanding of the hormonal basis of bone cell regulation.